Michael Huerta, MD, MPH and Alex Leventhal, MD, MPH
Recent events have drawn world attention to “mythological diseases” such as anthrax, plague and smallpox, which have been out of the spotlight for some decades. Much of our current knowledge of epidemic intervention and disease prevention was acquired over history through our experience with these very diseases, such that the sudden panic over the re-emergence of these historically well-known entities is perplexing. Over time, changes in the balance of the epidemiologic triangle have driven each of these disease systems towards a new equilibrium with which we are not familiar. While the pathogens may be similar, these are not the diseases of the past. These new disease systems are insufficiently described by the classic epidemiologic triangle, which lacks a dimension necessary for providing a valid model of the real-world effects of bioterror-related disease. Interactions within the classic epidemiologic triangle are now refracted through the prism of the global environment, where they are mediated, altered, and often amplified. Bioterror-associated diseases must be analyzed through the epidemiologic pyramid. The added dimension represents the global environment, which plays an integral part in the effects of the overall disease system. The classic triangle still exists, and continues to function at the base of the new model to describe actual agent transmission, but the overall disease picture should be viewed from the height of the fourth apex of the pyramid. The epidemiologic pyramid also serves as a practical model for guiding effective interventional measures.
Manfred S. Green, MD, PhD and Zalman Kaufman, MSc
The appearance of “new” infectious diseases, the reemergence of “old” infectious diseases, and the deliberate introduction of infectious diseases through bioterrorism has highlighted the need for improved and innovative infectious disease surveillance systems. A review of publications reveals that traditional current surveillance systems are generally based on the recognition of a clear increase in diagnosed cases before an outbreak can be identified. For early detection of bioterrorist-initiated outbreaks, the sensitivity and timeliness of the systems need to be improved. Systems based on syndromic surveillance are being developed using technologies such as electronic reporting and the internet. The reporting sources include community physicians, public health laboratories, emergency rooms, intensive care units, district health offices, and hospital admission and discharge systems. The acid test of any system will be the ability to provide analyses and interpretations of the data that will serve the goals of the system. Such analytical methods are still in the early stages of development.
Paul E. Slater, MD, MPH, Emilia Anis, MD, MPH and Alex Leventhal, MD, MPH, MPA
Because of its high case-fatality rate, its very high transmission potential, and the worldwide shortage of effective vaccine, smallpox tops international lists of over a dozen possible bioterror and biologic warfare agents. In a scenario involving aerosol variola virus release, tens to hundreds of first-generation cases would ensue, as would hundreds to thousands of subsequent cases resulting from person-to-person transmission. A smallpox outbreak in Israel must not be regarded as a doomsday event: the methods of smallpox outbreak control are known and will be implemented. The rapidity with which organized outbreak control measures are competently executed will determine how many generations of cases occur before the outbreak is brought under control. Planning, vaccine stockpiling, laboratory expansion, professional training and public education, all carried out well in advance of an epidemic, will minimize the number of casualties. The reinstitution of routine smallpox vaccination in Israel, as in other countries, must be given serious consideration, since it has the potential for eliminating the threat of smallpox as a bioterror agent.
Raymond Kaempfer, PhD, Gila Arad, PhD, Revital Levy, BA and Dalia Hillman, BA
Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock.
Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins.
Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined.
Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/a-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation.
Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.
Itzhak Braverman, MD, David Wexler, MD and Meir Oren, MD
Eyal Robenshtok, MD, Shay Luria, MD, Zeev Tashma, PhD and Ariel Hourvitz, MD
Atropine is the drug of choice for treatment of organophosphate (OP) nerve agent and insecticide intoxication and has been used for this indication for several decades. Adverse reactions to atropine may occur, and are of two types: toxic and allergic. Toxic reaction, the most common form, results from the anti-muscarinic effects of the drug. Since it is most probably related to interpersonal variation in sensitivity to atropine, toxic effects may appear at the usual therapeutic doses. The second type, allergic reaction, includes local manifestations, usually after the administration of eyedrops, and systemic reaction in the form of anaphylaxis. Since most patients manifest only a mild reaction, allergy testing is not performed and the prevalence of allergy to atropine is therefore not known. Severe allergic reaction to atropine is rare, as evidenced by the small number of case reports in the literature despite the drug's extensive use. Alternative anti-muscarinic drugs recommended for OP poisoning include glycopyrrolate and scopolamine. Glycopyrrolate is a peripheral anti-muscarinic drug that has been studied in comparison to atropine for many clinical indications, while scopolamine is an anti-muscarinic drug with both peripheral and central effects. An acceptable alternative regimen for patients with proven allergy to atropine is a combination of glycopyrrolate with centrally active drugs such as benzodiazepines or scopolamine.